New Ravidomycin Analogues, FE35A and FE35B, Apoptosis Inducers Produced by Streptomyces rochei.

The Journal of Antibiotics
1998.0

Abstract

Apoptosis is a physiological process by which cells undergo controlled cell death accompanied by nuclear condensation and fragmentation without loss of membrane integrity1,2). This phenomenon is generally observed during the development of lymphocytes and neutrophils3) in a hematopoietic system. In addition, neoplastic cells are often subjected to apoptosis when treated with anti-cancer drugs4,5). Since interleukin-1βconverting enzyme (ICE) proteases, particularly caspase-3, are activated during apoptosis, their overexpression inducing cell apoptosis is considered to play an important role in the initiation of apoptosis in variety of cell systems even though their molecular mechanisms are not well understood. During the course of our screening program for new antitumor antibiotics capable of inducing apoptosis in tumor cells, we isolated 6-hydroxytetrangulol6) as a caspase-3 inducer. Further investigation has resulted in the isolation of two novel substances belonging to the benzo [d] naphtho [1, 2-b] pyran-6-one group. We report herein the fermentation, isolation and structure determination of these two products designated FE35A (1) and FE35B (2).

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